Yuki Iijima1, Yosuke Hirotsu2, Kenji Amemiya2, Yoshihiko Ooka3, Hitoshi Mochizuki2, Toshio Oyama4, Takahiro Nakagomi5, Yoshinori Uchida5, Yoichi Kobayashi5, Toshiharu Tsutsui5, Yumiko Kakizaki5, Taichiro Goto5, Yoshihiro Miyashita5, Masao Omata6. 1. Lung Cancer and Respiratory Disease Center, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu City, Yamanashi 400-8506, Japan. Electronic address: iijipulm@jichi.ac.jp. 2. Genome Analysis Center, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu City, Yamanashi 400-8506, Japan. 3. Department of Gastroenterology, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba 260-8677, Japan. 4. Department of Pathology, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu City, Yamanashi 400-8506, Japan. 5. Lung Cancer and Respiratory Disease Center, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu City, Yamanashi 400-8506, Japan. 6. Genome Analysis Center, Yamanashi Central Hospital, 1-1-1 Fujimi, Kofu City, Yamanashi 400-8506, Japan; The University of Tokyo, 7-3-1 Hongo, Bunkyou-ku, Tokyo 113-8654, Japan.
Abstract
INTRODUCTION: Immunotherapy has become a treatment option for lung cancer. The utility of nivolumab as second-line treatment for non-small cell lung cancer has been proven, but predictive biomarkers influencing its efficacy remain unknown. METHODS: This study involved 14 patients who were treated with nivolumab from February 1 to September 30, 2016. The early response of the level of circulating tumour DNA (ctDNA) after starting nivolumab was evaluated to ascertain whether it could predict treatment outcome. RESULTS: Of the 14 patients, six were responders and eight were non-responders. DNA was analysed in both tumour tissue and plasma samples. Only somatic mutations confirmed by analysis of tumour tissue were defined as ctDNA. ctDNA was detected more often in the serial plasma samples of patients with high tumour volume (TV) (p = 0.02). ctDNA was detected in seven cases; basal and serial ctDNA analysis revealed that a decrease in allelic frequency (AF) of ctDNA showed high-level correspondence with a good durable response. When "2 weeks" was set as a clinically significant time point, changes in representative mutations of each case, defined as one of the highest baseline AF, showed 100% concordance with the response. CONCLUSIONS: In patients with high TV, plasma analysis of ctDNA, as validated by tumour tissue, suggested that a durable good response to nivolumab could be predicted within 2 weeks.
INTRODUCTION: Immunotherapy has become a treatment option for lung cancer. The utility of nivolumab as second-line treatment for non-small cell lung cancer has been proven, but predictive biomarkers influencing its efficacy remain unknown. METHODS: This study involved 14 patients who were treated with nivolumab from February 1 to September 30, 2016. The early response of the level of circulating tumour DNA (ctDNA) after starting nivolumab was evaluated to ascertain whether it could predict treatment outcome. RESULTS: Of the 14 patients, six were responders and eight were non-responders. DNA was analysed in both tumour tissue and plasma samples. Only somatic mutations confirmed by analysis of tumour tissue were defined as ctDNA. ctDNA was detected more often in the serial plasma samples of patients with high tumour volume (TV) (p = 0.02). ctDNA was detected in seven cases; basal and serial ctDNA analysis revealed that a decrease in allelic frequency (AF) of ctDNA showed high-level correspondence with a good durable response. When "2 weeks" was set as a clinically significant time point, changes in representative mutations of each case, defined as one of the highest baseline AF, showed 100% concordance with the response. CONCLUSIONS: In patients with high TV, plasma analysis of ctDNA, as validated by tumour tissue, suggested that a durable good response to nivolumab could be predicted within 2 weeks.
Authors: Andrew Georgiadis; Jennifer N Durham; Laurel A Keefer; Bjarne R Bartlett; Magdalena Zielonka; Derek Murphy; James R White; Steve Lu; Ellen L Verner; Finey Ruan; David Riley; Robert A Anders; Erika Gedvilaite; Sam Angiuoli; Siân Jones; Victor E Velculescu; Dung T Le; Luis A Diaz; Mark Sausen Journal: Clin Cancer Res Date: 2019-09-10 Impact factor: 12.531
Authors: Stephen J Bagley; S Ali Nabavizadeh; Jazmine J Mays; Jacob E Till; Jeffrey B Ware; Scott Levy; Whitney Sarchiapone; Jasmin Hussain; Timothy Prior; Samantha Guiry; Theresa Christensen; Stephanie S Yee; MacLean P Nasrallah; Jennifer J D Morrissette; Zev A Binder; Donald M O'Rourke; Andrew J Cucchiara; Steven Brem; Arati S Desai; Erica L Carpenter Journal: Clin Cancer Res Date: 2019-10-30 Impact factor: 12.531